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Ciliopathies are a group of genetic disorders caused by ciliary dysfunction. Thirty-five distinct multi-organ phenotypes have been recognized, with 187 genes associated. We performed a literature review of pancreatic involvement in ciliopathies and found that pancreatic disease is an uncommon phenotype described in only a handful of these genetic disorders. We present a case report of a pediatric patient with WDR19-related ciliopathy whose degree of pancreatic disease exceeds what has previously been reported in the literature for WDR19-related ciliopathies. WDR19 is one member of the nephronophthisis (NPHP)-related ciliopathy gene family and encodes an intra-flagellar transport protein (IFT144). Our patient presented with restrictive and obstructive lung disease, short rib thoracic dysplasia, end-stage renal disease (ESRD), developmental delay, hepatic fibrosis, and severe recurrent pancreatitis. Whole-exome sequencing (GeneDx) showed two likely pathogenic WDR19 variants in trans (maternally inherited: c.742G A, p.G248S; paternally inherited: c.617 T C, p.L206P). Among WDR19-related ciliopathies, pancreatic involvement is rarely reported and there have been no cases of severe, recurrent pancreatitis. Through this case report and literature review we hope to emphasize that pancreatic involvement is a rare yet important clinical phenotype to recognize in ciliopathies, especially in WDR19-related ciliopathies.

Background Assessment of fluid status in neonatal dialysis has largely focused on traditional tools including clinical assessment, serial weights, and blood pressure (BP) measurements. However, in infants on kidney replacement therapy, the assessment of fluid overload is problematic due to errors in weight assessment, subtlety of physical exam findings, and inaccuracy of non-invasive BP measurements. Case summary In this presentation of a neonate with bilateral renal agenesis requiring kidney replacement therapy, the treating team assessed a number of variables in determining the ultrafiltration prescription for dialysis across 2 modalities (hemodialysis and continuous kidney replacement therapy). Complications Fluid overload, cardiomegaly, and worsened respiratory status occurred when attempting to assess the neonate’s fluid status by traditional markers (weights, blood pressures, physical exam findings). B-type natriuretic peptide (BNP) was obtained and was noted to correlate with the degree of fluid overload. Key management points Compared to traditional tools for assessment of fluid status in pediatric dialysis, BNP assisted the medical team in optimizing the volume status of the subject and determining optimal daily ultrafiltration goals. Due to the rapid release in response to myocardial stretch and the lack of kidney clearance of the peptide, BNP may represent an objective, timely, and reliable index of volume status in the pediatric dialysis patient.

Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology—Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals). This report summarizes the discussions on the identification and implementation of the SONG-Kids core outcomes set. Four themes were identified; survival and life participation are common high priority goals, capturing the whole child and family, ensuring broad relevance across the patient journey, and requiring feasible and valid measures. Stakeholders supported the inclusion of mortality, infection, life participation, and kidney function as the core outcomes domains for children with chronic kidney disease.

Background:Current pediatric International Society for Peritoneal Dialysis guidelines for initial treatment of peritoneal dialysis (PD)-associated peritonitis suggest either monotherapy with cefepime or double therapy with first-generation cephalosporin or glycopeptide and ceftazidime or aminoglycoside. When using vancomycin, the intraperitoneal (IP) recommended pediatric loading dosage is 1000 mg/L of dialysate. This is based on adult pharmacokinetic (PK) studies and roughly translates to the adult recommendation where 30 mg/kg in 2 L is approximately 1000 mg/L. However, since the dialysate volume in pediatric patients is normalized to body surface area and not weight, the current recommended dosing can result in high vancomycin exposure in children. Vancomycin can potentially cause adverse effects. We aimed to determine if the IP vancomycin dosing of 1000 mg/L was causing elevated vancomycin levels and to offer possible dosing recommendations based on PK modeling and simulation.Methods:Retrospective review of pediatric patients who had been treated with IP vancomycin for PD-associated peritonitis. Vancomycin levels obtained for clinical monitoring were analyzed using NONMEM to generate population and individual (empiric Bayesian) estimates of vancomycin PK parameters and estimated peak levels. Predicted vancomycin peaks were also simulated from virtual pediatrics patients 3–70 kg following various dosing strategies.Results:Six episodes of peritonitis in three patients were analyzed. In the two episodes treated with 1000 mg/L, the first vancomycin levels (h post) were 95.6 ug/mL (3) and 49 (33) and following 500 mg/L were 33.2 (11), 30.2 (11), 23.6 (24), and 22.1 (11). All patients were cured of their peritonitis without the need for catheter removal. Based on our population PK model, a 1000 mg/L IP vancomycin loading dose will typically result in peak > 50 mg/L in patients weighing 60 mg/L in patients Conclusion:The data suggest that a loading dose of vancomycin 1000 mg/L leads to higher than desired vancomycin levels and should be lowered. A 500 mg/L loading dosing appears more appropriate and needs further study.

RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) guideline on CKD presented an international classification system that ranks patients' risk for CKD progression. Few data on children informed guideline development STUDY DESIGN: Observational cohort study SETTINGS AND PARTICIPANTS: Children aged 1-18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. PREDICTOR: Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio (mg/mg)) at study entry OUTCOME: A composite event of renal replacement therapy, 50% reduction of estimated GFR (eGFR), or eGFR 2.0 at study entry. Six ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44 and 15-29 ml/min/1.73m(2)) and UPCR categories (2.0) described the risk continuum. Median times to event ranged from >10 years for eGFR 45-90 and UPCR 2. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the ten subsample validation models. LIMITATIONS: Observational study, utilized cross validation rather than external validation CONCLUSION: CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.

Background and objectives Steroid-resistant nephrotic syndrome overwhelmingly progresses to ESRD. More than 30 monogenic genes have been identified to cause steroid-resistant nephrotic syndrome. We previously detected causative mutations using targeted panel sequencing in 30% of patients with steroid-resistant nephrotic syndrome. Panel sequencing has a number of limitations when compared with whole exome sequencing. We employed whole exome sequencing to detect monogenic causes of steroid-resistant nephrotic syndrome in an international cohort of 300 families. Design, setting, participants, & measurements Three hundred thirty-five individuals with steroid-resistant nephrotic syndrome from 300 families were recruited from April of 1998 to June of 2016. Age of onset was restricted to Results In 74 of 300 families (25%), we identified a causative mutation in one of 20 genes known to cause steroid-resistant nephrotic syndrome. In 11 families (3.7%), we detected a mutation in a gene that causes a phenocopy of steroid-resistant nephrotic syndrome. This is consistent with our previously published identification of mutations using a panel approach. We detected a causative mutation in a known steroid-resistant nephrotic syndrome gene in 38% of consanguineous families and in 13% of nonconsanguineous families, and 48% of children with congenital nephrotic syndrome. A total of 68 different mutations were detected in 20 of 33 steroid-resistant nephrotic syndrome genes. Fifteen of these mutations were novel. NPHS1, PLCE1, NPHS2, and SMARCAL1 were the most common genes in which we detected a mutation. In another 28% of families, we detected mutations in one or more candidate genes for steroid-resistant nephrotic syndrome. Conclusions Whole exome sequencing is a sensitive approach toward diagnosis of monogenic causes of steroid-resistant nephrotic syndrome. A molecular genetic diagnosis of steroid-resistant nephrotic syndrome may have important consequences for the management of treatment and kidney transplantation in steroid-resistant nephrotic syndrome.

Therapeutic plasma exchange is an extracorporeal treatment modality that removes systemic circulating pathologic factors or replaces absent plasma components and plays a role in many nephrologic conditions. It presents a number of technical challenges in the pediatric population but has become an increasingly common practice in pediatric nephrology over the past several decades. While prospective evidence is often lacking, our increased understanding of the molecular pathogenesis underlying many pediatric renal diseases provides sound reasoning for the use of plasma exchange in treating these conditions. This review will present the currently accepted indications for plasma exchange in children, the technical aspects of the procedure and its potential complications.

Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naive patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy. One-hundred sixteen pediatric ESA-naive subjects (aged 1–18 years) with CKD stages 3–5D and hemoglobin (Hb)

Peritonitis is the most common complication and the leading cause of death in pediatric peritoneal dialysis (PD) patients. According to the most recent data available from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), approximately 25% of pediatric PD patients who die succumb to infection. There are no reported cases of Mycobacterium tuberculosis (MTB) or Mycobacterium avium-intracellulare peritonitis in the NAPRTCS registry. With an increasing incidence of MTB worldwide and the impairment of cellular immunity in chronic renal failure patients, it is not surprising that mycobacterium peritonitis can occur in PD patients. We report two pediatric PD patients with mycobacterial peritoneal infection diagnosed over an 11-year period at our institution. One patient presented with a malfunctioning Tenckhoff catheter and again 3 years later with hyponatremia and ascites. The other presented with recurrent culture-negative peritonitis. These cases illustrate the importance of more extensive evaluation of PD complications, to include evaluation for mycobacterium with special media or peritoneal biopsy, in the above clinical settings if the routine work-up is unrevealing.

Interpopulation variability of drug pharmacokinetics (PK) has been described. For example, the systemic clearance of nifedipine is higher in Mexicans than Caucasians. African-Americans have a lower cyclosporine bioavailability than Caucasians. Limited data are available in the Latino population. Under identical conditions, we compared the PK profile of Neoral (cyclosporine for microemulsion) obtained in stable pediatric renal transplant recipients of Latino and Caucasian origin. A slightly lower area under the curve (AUC) when corrected for dose per body surface area or per kilogram of body weight was observed in Caucasians compared with Latinos. This difference was more pronounced in the younger age group (< 12 years) with a higher peak-to-trough ratio. However, the Caucasians required a higher dosage of Neoral than the Latinos to achieve that same AUC. There was no difference between the groups in the time (tmax) to reach maximal concentration (Cmax) of Neoral. A higher apparent clearance of the drug was observed in the Caucasians compared with the Latinos, especially in the younger age group. No differences in pre- and post-dose levels were observed between the two groups. These differences might affect dose adjustment between the two subpopulations.

Cross-cultural medicine is a field that describes how disparate value and belief systems concerning health and disease affect the delivery of health care. This report describes the conflict between a Hmong immigrant family and the Western medical establishment over the care of their child with end stage renal disease [ESRD]. The health care providers, social service agencies and medical center failed to adequately respond to the needs of the family. The medical staff [nephrologist, nurse coordinator, dietician, social worker, and CPS worker] worked with a transcultural nurse, Hmong community health worker and the family, to design and negotiate a treatment plan that would be acceptable to the family and the health care team. Trust was reestablished between the family and the healthcare providers and the medical outcome for the child improved.

Objective. In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured serum procalcitonin levels, a recently described marker of infection. We compared it with other commonly used inflammatory markers and evaluated its ability to predict renal involvement as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. Methods. Serum C-reactive protein, leukocyte counts, and procalcitonin levels were measured in 80 children, 1 month to 16 years of age, admitted for suspected pyelonephritis. Renal involvement was assessed by 99mTe-DMSA scintigraphy in the first 5 days after admission. The examination was repeated at least 3 months later if the first result was abnormal. Results. In lower UTI, the mean procalcitonin (PCT) was 0.38 μg/L ± 0.19 compared with 5.37 μg/L ± 1.9 in pyelonephritis. In these two groups, respectively, leukocyte counts were 10939/mm3 ± 834 and 17429/mm3 ± 994, and C-reactive protein (CRP) levels were 30.3 mg/L ± 7.6 and 120.8 mg/L ± 8.9. When inflammatory markers were correlated to the severity of the renal lesion as ranked by DMSA scintigraphy, we found a highly significant correlation with plasma levels of PCT, but borderline significance with CRP and none with leukocyte counts. Patients without vesicoureteral reflux had a mean PCT of 5.16 μg/L ± 2.33, which was not significantly different from that in patients with reflux who had a mean PCT of 5.76 μg/L ± 3.49. For the prediction of renal lesions at admission, CRP had a sensitivity of 100% and a specificity of 26.1%. The sensitivity and specificity of PCT were 70.3% and 82.6%, respectively. Conclusion. We conclude that serum PCT levels were increased significantly in children with febrile UTI when renal parenchymal involvement (assessed by DMSA scintigraphy) was present and allowed for prediction of patients at risk of severe renal lesions.

Objective: To investigate the renal handling of carnitine in preterm and term ill neonates. Methods: We studied the fractional tubular reabsorption of carnitine and the proximal renal tubular function of infants in the first week of life who were receiving very little or no carnitine in their diets. Results: Mean plasma levels were low: total carnitine was 16.4 ± 7.0 μmol/L, free carnitine was 9.2 ± 5.0 μmol/L, and acylcarnitine was 7.2 ± 4.1 μmol/L. The most premature group of neonates (gestation age, 26 to 31 weeks) had a fractional tubular reabsorption rate of free carnitine of 94.3% ± 3.3%, which was lower than in the other two groups (98.1% ± 2.4% for gestational age 32 to 36 weeks, p = 0.001; and 99.2% ± 0.6% for gestational age 37 to 42 weeks, p = 0.002). In all patients the fractional tubular reabsorption of acylcarnitine was lower than that of free carnitine, indicating possible tubular secretion of acylcarnitine. It correlated with the total plasma carnitine levels ( r = 0.53; p = 0.002). The fractional tubular reabsorption of free carnitine also correlated with gestational age ( r = 0.60; p Conclusions: Ill neonates have a fractional tubular reabsorption rate of free carnitine within the normal range. It increases with gestational age, and has the same maturation rate as the other known indexes of proximal tubular function. (J PEDIATR 1995;127:975-8)

To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.Annualized GFR change in subjects with ARPKD was -1.4 mL/min/1.73 m(2) (-6%), with greater decline in subjects age ≥ 10 years (-11.5%). However, overall rates of GFR decline did not differ significantly in subjects with ARPKD vs controls. There were no significant differences in rates of HTN or left ventricular hypertrophy, but subjects with ARPKD had a greater percent on ≥ 3 blood pressure medications (32% vs 0%, P.0001), more angiotensin-converting enzyme inhibitor use (82% vs 27% vs 36%, P.0005), and less proteinuria (urine protein: creatinine = 0.1 vs 0.6, P.005).This study reports rates of GFR decline, HTN, and proteinuria in a small but well-phenotyped ARPKD cohort. The relatively slow rate of GFR decline in subjects with ARPKD and absence of significant proteinuria suggest that these standard clinical measures may have limited utility in assessing therapeutic interventions and highlight the need for other ARPKD kidney disease progression biomarkers.

We designed a prospective study to evaluate the ability of dimercaptosuccinic acid cortical scintigraphy and ultrasonography to detect renal parenchymal lesions in children with pyelonephritis. One hundred eleven patients 1 week to 16 years of age (median 5.5 months) with a urine culture positive for pathogens were included in the study; cortical scintigraphy and ultrasonography were repeated in 25 children after a mean follow-up of 10.5 months. Cortical scintigraphy showed renal changes in 74 children (67%), and ultrasonography showed renal changes in 39 (35%) (p < 0.001); results of the two examinations were discordant in 49 patients (kappa = 0.19). Children more than 1 year of age had a higher incidence of renal lesions than did younger children (85% vs 66%; p = 0.04). The presence of inflammatory signs (erythrocyte sedimentation rate or C-reactive protein) had an 89% sensitivity and a 25% specificity in identifying renal lesions. Among children with renal changes, vesicoureteric reflux was present in 39%. At follow-up examination, 16 children (64%) had scars. Thus we found a high incidence of renal involvement in children with pyelonephritis. We found that cortical scintigraphy is more sensitive than ultrasonography in detecting renal changes, and we believe that it should be added to the initial examination of children with suspected pyelonephritis. (J PEDIATR 1994;124:17-20)

Background and objectives: Proteinuria is associated with chronic kidney disease (CKD), and heavy proteinuria predicts a rapid decline in kidney function. However, the epidemiologic distribution of this important biomarker study is not well described in the pediatric CKD population. Design, setting, participants & measurements: This cross-sectional study of North American children with CKD examined the association of proteinuria among the baseline clinical variables in the cohort. Urinary protein-to-creatinine ratios (Up/c) were used to measure level of proteinuria. Results: Of the 419 subjects studied, the median GFR as measured by iohexol disappearance (iGFR) was 42 ml/min per 1.73 m2, median duration of CKD was six yr, and glomerular diseases accounted for 22% of the CKD diagnoses. Twenty-four percent of children had normal range (Up/c 2.0). A decrease in iGFR was associated with an increase in Up/c. At any level of GFR, a higher Up/c was associated with a glomerular cause of CKD and non-Caucasian race. Among subjects with a glomerular cause of CKD, Up/c was lower in subjects reporting utilization of renin-angiotensin system (RAS) antagonists (median Up/c = 0.93) compared with those who did not (median Up/c = 3.78). Conclusions: Proteinuria is associated with level of iGFR, cause of CKD, and race. The longitudinal study design of Chronic Kidney Disease in Children (CKiD) cohort study and the large number of subjects being studied has created an opportunity to better define the association between proteinuria and CKD progression.

To assess depression in children with chronic kidney disease and to determine associations with patient characteristics, intellectual and educational levels, and health-related quality of life (HRQoL).Subjects aged 6-17 years from the Chronic Kidney Disease in Children cohort study completed the Children's Depression Inventory (CDI), Wechsler Abbreviated Scales of Intelligence, Wechsler Individual Achievement Test-II-Abbreviated, and the Pediatric Inventory of Quality of Life Core Scales 4.0. Regression analyses determined associations of CDI score and depression status with subject characteristics, intellectual and educational levels, and HRQoL. A joint linear mixed model and Weibull model were used to determine the effects of CDI score on longitudinal changes in glomerular filtration rate and time to renal replacement therapy.A total of 344 subjects completed the CDI. Eighteen (5%) had elevated depressive symptoms, and another 7 (2%) were being treated for depression. In adjusted analyses, maternal education beyond high school was associated with 5% lower CDI scores (estimate, 0.95; 95% CI, 0.92-0.99). Depression status was associated with lower IQ (99 vs 88; P = .053), lower achievement (95 vs 77.5; P.05), and lower HRQoL by parent and child reports (effect estimates, -15.48; 95% CI, -28.71 to -2.24 and -18.39; 95% CI, -27.81 to -8.96, respectively). CDI score was not related to change in glomerular filtration rate.Children with depression had lower psychoeducational skills and worse HRQoL. Identifying and treating depression should be evaluated as a means of improving the academic performance and HRQoL of children with chronic kidney disease.

We report three cases of neonatal herpes simplex virus (HSV) infection presenting as fulminant hepatitis. None of the patients had clear risk factors for HSV infection and they all died. Antiviral treatment for HSV is currently available but must be administered early in the course of the disease before irreversible liver tissue damage is present. Since the diagnosis may be difficult to establish, we wish to draw the attention of clinicians to the presentation of neonatal HSV infection and suggest that in such cases viral cultures, including culture of liver tissue, should be obtained early and antiviral treatment administered while awaiting the culture results.

Background Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium × phosphorus (Ca × P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca × P product than calcitriol and has been used effectively in adult hemodialysis patients. Study Design Double blind, placebo-controlled. Setting & Participants Hemodialysis units and pediatric subjects receiving hemodialysis. Intervention After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 μg/kg if initial intact parathyroid hormone [iPTH] level 500 pg/mL [ng/L]). The dose was increased by 0.04 μg/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca × P product greater than 75 mg 2 /dL 2 (>6.04 mmol 2 /L 2 ). Outcomes & Measurements Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca × P product. Results 60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group ( P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca × P product values in either group. Limitations Low power to detect differences in safety between groups and a short-term study. Conclusion Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca × P product values during the course of the study.

Nephrogenic systemic fibrosis (NSF) is a rare condition that always occurs after acute or chronic renal failure with or without dialysis. The vast majority of cases in the literature are adults, and postmortem findings have been reported in only 5 cases. We report a 15-year-old male who developed NSF with multiorgan involvement after successful treatment of renal lymphoma and a subsequent sacral Ewing's sarcoma, and end-stage renal disease treated with hemodialysis. At autopsy, he was found to have diffuse dural osseous metaplasia, transmural bronchiolar fibrosis, diaphragmatic central tendon fibrosis, and fibrous plaques of the mitral valve. These previously unreported findings expand the spectrum of multiorgan involvement in NSF providing additional evidence that it is an emerging systemic disorder.

The general belief about the relation between risk of renal sequelae after pyelonephritis and age is that infants are at highest risk and children older than 5 years at lower risk. This assumption has led to differences in treatment based on age. The aim of this prospective study was to investigate the occurrence of renal lesions in children aged 0-16 years.Between May, 1994, and January, 1996, all children aged 0-16 years who were admitted to our department with a diagnosis of probable pyelonephritis and a positive urine culture were included in this prospective study. All patients received antibiotics for 7-21 days. During the acute phase of urinary-tract infection, scintigraphy with technetium-99m-dimercaptosuccinic acid (DMSA) and ultrasonography were done. Voiding cystourethrography was undertaken at least 6 weeks after the end of antibiotic treatment. When scintigraphy showed renal parenchymal lesions, repeat scintigraphy was done after at least 2 months to assess the progression of renal lesions. For the analysis, children were grouped by age according to presumed risk of renal sequelae after pyelonephritis: high risk (1 year), moderate risk (1-5 years), low risk (5 years).201 patients were enrolled in the study (1191 year, 47 aged 1-5 years, 355 years). During the acute phase of urinary-tract infection, renal lesions were found in 66 (55%) infants under 1 year, in 37 (79%) children aged 1-5 years, and in 24 (69%) children older than 5 years. Of these 127 children, 108 underwent repeat scintigraphy after an average of 3 months (501 year, 36 aged 1-5 years, 225 years). Overall, renal scars were found on repeat scintigraphy in 20 (40%) infants under 1 year, in 31 (86%) children aged 1-5 years, and in 14 (64%) children older than 5 years. 38 (36%) of these 65 patients had vesicoureteric reflux. Among 88 children who had a first documented urinary-tract infection and underwent repeat scintigraphy, renal scars were found in 20 (43%) under 1 year, in 26 (84%) aged 1-5 years, and in eight (80%) older than 5 years.This study did not confirm the conventional view that the risk of renal scars after pyelonephritis diminishes with age. We believe that all children, irrespective of age, will benefit from any measure that prevents the development of renal sequelae.

This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values400 pg mL(-1), calcium levelsor = 10.5 mg dL(-1) and calcium x phosphorus product valuesor = 70 mg2 dL(-2) were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5-1.5 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca11.0 mg dL(-1), or Ca x P75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutiveor = 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L(-1) in the calcitriol group and increased from 547 to 669 IU L(-1) in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x P75 mg2 dL(-2)) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus6.5 mg dL(-1) occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels10.5 mg dL(-1) were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product.

Autosomal-recessive polycystic kidney disease (ARPKD) can cause renal failure and portal hypertension in children. Portal hypertension may complicate the course of renal transplantation (Tx). We report the successful outcome of a patient with end-stage renal disease (ESRD) and portal hypertension treated with transjugular intrahepatic portosystemic shunt (TIPS), a minimally invasive endovascular technique of portosystemic shunt, prior to renal Tx.

In vivo and in vitro findings have shown that plasma of patients with idiopathic nephrotic syndrome (INS) contain factors that increase glomerular permeability to proteins. The effects of these factors on proteoglycan synthesis by glomerular cells are unknown. To investigate the effect of plasma from patients with INS (n = 23) and other glomerulopathies (n = 12) on the amount of proteoglycans synthesized by cultured rat mesangial cells and human glomerular epithelial cells, glomerular cells were cultured for 24 h with plasma from patients or control subjects, and incorporation of Na2(35)SO4 in chondroitin dermatan sulfate and heparan sulfate was assessed using a cationic nylon membrane. The mean ratio of glycosaminoglycan produced by rat mesangial cells when in contact with plasma (5%) from INS patients to the amount produced when in contact with control plasma was 0.70+/-0.06. The mean ratio of heparan sulfate was 0.58+/-0.08. The decrease of heparan sulfate production was present in the cellular and in the extracellular fraction. It was observed when the cells were in contact with plasma from patients in relapse but not when in remission. No decrease of heparan sulfate production was observed with four of the five patients with membranous glomerulonephritis (ratio of 1.27+/-0.03), IgA nephropathy (n = 5, ratio of 1.27+/-0.03), and membranoproliferative glomerulonephritis (n = 2, ratio of 1.39+/-0.34). When human glomerular epithelial cells were exposed to 5% plasma from INS patients in relapse (n = 9), the mean ratio of heparan sulfate was 0.62+/-0.06 in the cellular fraction and 0.72+/-0.08 in the medium. When in contact with plasma from patients in remission, no difference of glycosaminoglycan production was observed. A factor present in plasma from patients with INS during initial episodes or relapses is able to decrease the proteoglycan production of glomerular cells.

Recent studies have revealed the potential importance of the extracellular matrix (ECM) in the modulation of mesangial cell (MC) function. Interleukin-6 (IL-6) is produced by MCs and was shown to induce MC proliferation, acting as an autocrine growth factor. Heparin is a known inhibitor of MC proliferation. It was shown to modulate ECM synthesis by cultured MCs. The action of heparin on IL-6 synthesis by MCs is presently unknown. We investigated the effect of heparin on IL-6 production when MCs were cultured with or without type-IV collagen, a major constituent of ECM. When MCs were cultured without coating, heparin significantly decreased their IL-6 production; on type-IV collagen, heparin had no significant effect. When tumor necrosis factor alpha (TNF-alpha) was used to stimulate the cells to produce IL-6, heparin was able to decrease the stimulatory effect of TNF-alpha when the cells were cultured on plastic but not when in contact with type-IV collagen. Thus we conclude that heparin has an inhibitory effect on IL-6 secretion by MCs that is prevented by type-IV collagen.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis and vasculopathy of the skin and visceral organs. Scleroderma renal crisis (SRC), the most acute and life threatening complication, occurs in 10–20% of adult patients with SSc and has not been reported in children. A 10-year-old girl was diagnosed with SSc when she presented with weakness and skin thickening. She had positive ANA and anti-Scl 70. Renal function, urinalysis, and blood pressure were normal. She was treated with steroids, penicillamin and methotrexate as well as amlodipine for Raynaud's phenomenon, but her diffuse skin thickening and contractures progressed and she became wheelchair bound and had poor growth despite nutrition through a G-tube. At age 15 (weight 28 kg), when evaluated for abdominal pain, she was found to have acute renal failure (BUN 54 mg/dl, creatinine 2.2 mg/dl) and hypertension. Despite therapy with enalapril, serum creatinine continued to rise and she became oligoanuric, requiring initiation of hemodialysis. BP was controlled with enalapril and dialysis but she remained dialysis dependent. Steroid therapy was discontinued and replaced by low dose cyclosporine. Enalapril was replaced by losartan because of leukopenia and BP remained normal. Over the next 2 years, she was treated with hemodialysis and did not experience any complications. She progressively had an outstanding overall clinical improvement, marked skin softening, and was able to walk independently. Renal function did not improve. 28 months after the SRC, she received LRD renal transplant. Immunosuppression included cyclosporine, mycophenolate and prednisone. Creatinine 2 months post-transplant is 0.7 mg/dl. SRC in children may progress to end-stage renal disease but can be treated successfully with dialysis and transplantation without significant complications.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is an important advance for the treatment of critically ill patients. A major problem with CRRT is the need for systemic anticoagulation with heparin. Recently we have adapted a new form of regional citrate anticoagulation for children requiring CRRT. This procedure uses continuous venovenous hemodiafiltration (CVVHDF). Anticoagulation is achieved in the extracorporeal circuit by infusing citrate directly into the blood as it leaves the patient. The citrate acts as an anticoagulant by chelating calcium. The effect of citrate is reversed in the patient's circulation by infusing calcium chloride, so that the patient's coagulation system is unaffected by the procedure.